1. Technical Field of the Invention
The present invention relates generally to microfluidic devices, and particularly to fabrication and adhesion of microfluidic devices.
2. Description of Related Art
In recent years, microfluidic device technologies, also referred to as microfluidics and Lab-on-a-Chip technologies, have been proposed for a number of applications, including chemical analysis for pharma, biotechnology, fuel cells, etc. Microfluidic devices hold great promise for many applications, particularly in applications that employ rare or expensive fluids, such as proteomics and genomics. The small size of the microfluidic devices allows for the analysis of minute quantities of sample. Having the potential to integrate functions such as sample collection, sample preparation, sample introduction, separation, detection, and compound identification in one device, microfluidic devices such as μ-total analysis systems (μ-TAS) have come to represent the main focus of academic and industrial laboratories research relating to chemical analysis tools or clinical diagnostic tools.
Microfluidic devices having integrated components, e.g., for sample preparation, separation and detection compartments have been proposed in a number of patents. See, e.g., U.S. Pat. No. 5,500,071 to Kaltenbach et al., U.S. Pat. No. 5,571,410 to Swedberg et al., and U.S. Pat. No. 5,645,702 to Witt et al. Because such microfluidic devices have a relatively simple construction, they are in theory inexpensive to manufacture.
Microfluidic devices may be adapted to employ or carry out a number of different separation techniques. Capillary electrophoresis (CE), for example, separates molecules based on differences in the electrophoretic mobility of the molecules. Typically, microfluidic devices employ a controlled application of an electric field to induce fluid flow and or to provide flow switching. In order to effect reproducible and/or high-resolution separation, a fluid sample “plug,” a predetermined volume of fluid sample, must be controllably injected into a capillary separation column or conduit. For fluid samples containing high molecular weight charged biomolecular analytes such as DNA fragments and proteins, microfluidic devices containing a capillary electrophoresis separation conduit a few centimeters in length may be effectively used in carrying out sample separation of small volumes of fluid sample having a length on the order of micrometers. Once injected, high sensitivity detection such as laser-induced fluorescence (LIF) may be employed to resolve a separated fluorescently labeled sample component.
For samples containing analyte molecules with low electrophoretic differences, such as those containing small drug molecules, the separation technology of choice is often based on chromatography. Chromatographic separation occurs when a mobile phase carries sample molecules through a chromatography bed (stationary phase) where sample molecules interact with the stationary phase surface. The velocity at which a particular sample component travels through a chromatography bed depends on the component's partition between mobile phase and stationary phase.
There are many chromatographic techniques known in the art. For example, in reverse phase liquid chromatography, where the stationary phase offers a hydrophobic surface and the mobile phase is usually a mixture of water and organic solvent, the least hydrophobic component moves through the chromatography bed first, followed by other components, in order of increasing hydrophobicity. In other words, the chromatographic separation of sample components may be based on hydrophobicity. In isocratic liquid chromatography, the content of the mobile phase is constant throughout the separation. Gradient liquid chromatography, on the other hand, requires the content of the mobile phase to change during separation. Gradient liquid chromatography not only offers high resolution and high-speed separation of wide ranges of compounds, it also allows injection of large sample volumes without compromising separation efficiency. During the initial period when the sample is introduced, the mobile phase strength is often kept low, and the sample is trapped at the head of the liquid chromatography column bed. As a result, interfering moieties such as salts are washed away. In this regard, gradient liquid chromatography is suited to analyze fluid samples containing a low concentration of analyte moieties.
Such microfluidic devices have typically been fabricated by etching grooves, holes, and other features on the surface of a rigid or flexible substrate. The resulting patterned substrate is capped and bonded with another substrate, forming channels where gases or liquids move to accomplish the various applications the devices are designed for. Conventional rigid substrate materials include silicon, glass, metals. Conventional flexible substrate materials include thermoplastic materials, such as PDMS (polydimethysiloxane) and polyacrylates, thermosets, such as epoxides, and solution-processed polymers, such as polyimides.
Flexible substrate materials are typically preferred to rigid substrate materials due to their versatility, low cost and the diversity of processing methods they afford, such as thermoforming, injection molding, etc. Of the available flexible substrate materials, certain polymeric thermoplastic substrate materials have been suggested for use in microfluidic devices due to desirable properties, such as high mechanical modulus, toughness, low thermal distortion and high chemical resistance. For example, such polymeric materials can include polyaryl-ether-ketones (PAEK), such as polyether-ether-ketone (PEEK), polyether-ketone-ether-ketone-ketone (PEKEKK) and polyether-ketone-ketone (PEKK).
For example, U.S. Pat. No. 6,267,884 to Myers (hereinafter referred to as Myers), which is hereby incorporated by reference, discusses using a polymeric substrate material, such as PEEK, to form a capillary liquid chromatography column. The Myers capillary column is formed by molding one plate of the substrate material to produce the capillary column, placing beads within the capillary column and bonding a second plate to the first plate to seal the capillary column.
Although PEEK is mentioned in Myers as a possible substrate material, in practice, PAEK thermoplastic materials have presented difficult manufacturing challenges. One challenge has been that the melt-processing equipment and tools necessary to process PAEK are expensive due to the fact that PAEK is a high-temperature melting engineering thermoplastic. Moreover, the high melting point temperature (Tm) of PAEK has also made it difficult to optimize the process conditions.
In addition, traditional bonding materials used for PAEK devices, such as epoxides and acrylates, are not chemically inert to the solvents and temperatures that are commonly required in microfluidic applications, such as High Performance Liquid Chromatography (HPLC). For example, as described in a pamphlet produced on a web page of the Westlake Plastics Company (www.westlakeplastics.com), traditional adhesive agents have included various epoxides and cyanoacrylates. Such traditional adhesive agents are not sufficiently resistant to solvents, such as methyl sulfoxide (DMSO), dimethyl formamide (DMF) and N-methyl pyrrolidone (NMP). Furthermore, PAEK devices have also proved resistant to many of the traditional bonding materials. Therefore, it has been difficult to bond PAEK to PAEK and PAEK to other materials. What is needed is a method of bonding PAEK substrates for use in fabricating microfluidic devices, such as HPLC device.